1. Field of the Invention
The object of the invention is a diluent and disintegrating composition. It also covers a method for obtaining this composition as well as its industrial use, for the manufacture of solid shapes.
2. Description of the Prior Art
By the expression "solid shapes" is meant every presentation of powder(s) in the form of tablets, pellets, capsules, microspheres or granules. The solid shapes consist mainly of inert materials, grouped together under the term of excipients, as a complement to one or more active pharmaceutical, cosmetic, foodstuff, chemical or agro-chemical substances, such as flavourings, perfumes, detergents, pesticides, antibiotics, enzymes, vitamins. These excipients are generally classified according to their principal function(s), that is how diluents, or filling agents, binders which ensure cohesion of the ingredients, disintegrators which enable the destruction of the physical integrity of the solid shapes when these are placed in an appropriate fluid are distinguished. Other excipients can be added in parallel, particularly lubricants in order to improve the flowing properties of the powders. A good powder diluent must possess the following properties:
chemical compatibility with the active substance, PA1 free flow, to enable an even filling of the matrices in the modern high rate shaping machines, PA1 granulometry adapted to that of the active substance, in order to ensure a constant dosage, PA1 absence of dust, to facilitate handling, to avoid clogging and to limit the risks of explosion, PA1 high density, to promote the flow and limit the size of the final solid shape, PA1 cohesion, to ensure the physical stability of the solid shapes. PA1 during an elastic deformation, the deformation disappears when the force ceases to be applied. PA1 This deformation is not favourable to producing tablets, since the particles regain their initial state at the end of compression. This is particularly the case for natural starches. PA1 during a plastic deformation, on the other hand, the deformation persists when the force ceases to be applied, this being entirely favourable to the production of tablets.
A good disintegrator must ensure a rapid availability of the active substances, whilst having satisfactory rheological properties.
The formulator wishes to have a principal excipient possessing optimum properties, which he will make up as a function of the characteristics of the solid shape which he wishes to develop, with one or more secondary excipients. There does not exist any universal excipient having all the previously described properties.
Starch and its derivatives form part of the chosen excipients, giving a wide spectrum of performance for the formulation of solid shapes.
In the natural state, starch comes in the form of granules, the diameter of which varies approximately between 1 and 100 .mu.m.
Its availability and its low cost, as well as its natural origin are the principal factors favouring its use. The majority of the commercial starches come from maize, but wheat and potato are also significant sources. Other sources are known, like rice, manioc, peas. Starch consists of two types of .alpha.-D-glucose polymers, amylose and amylopectin, which have a different structure : amylose is a linear polymer, whilst amylopectin possesses a ramified structure.
Most of the starches, coming from maize, from wheat or from potato, contain 18 to 28% of amylose.
In the manufacture of solid shapes, starch is used as diluent, binder or disintegrator.
Natural starch offers, on its own, a limited number of applications. Indeed, when it is used as a direct compression diluent, its compressibility is insufficient to enable the manufacture of tablets of satisfactory hardness.
Actually, in the particular case of compression, the particles undergo a deformation, which can be of different types according to their nature : elastic or plastic deformation.
Moreover, natural starch possesses poor flow properties, which makes it inadvisable in formulations for direct compression. This is due to the small size of its particles as well as its low density. The fluidity of the formulations is an essential criterion on which depends the weight uniformity of the completed tablets. On the other hand, natural starch possesses good disintegrating properties. Indeed, starch granules swell in the presence of water, which causes the rupture of the structure in which they are contained, and therefore its disintegration.
Natural starch can be modified in a simple and inexpensive manner by a thermal process causing the rupture of the granules and a partial hydrolysis of the polymeric chains. A pre-gelatinised starch is then produced which, in powder form and for a selected granulometry, is a good flowing and compressing product, but possessing a practically zero disintegrating power. It is preferably used as a binder for powders.
Chemical modifications, such as reticulation, described in the U.S. Pat. No. 4,369,308, can be made to pre-gelatinised starch, but these lead to a poor quality disintegrating agent.
Taking account of the fact that the properties of pre-gelatinised starch and of natural starch are diametrically opposite but nevertheless jointly required in numerous solid shapes, a simple mixture of the two powders would have to be considered. However, these two starches possess granulometries which are very different from each other, which causes a rapid "unmixing" of the powders from the slightest handling, and a very varying homogeneity of the final solid shape, which is industrially unacceptable.
In the patent FR 1, 583 232, a compacting process leading to a partially pre-gelatinised starch has therefore been proposed. The product produced according to this procedure, and marketed under the name STARCH 1500.RTM., possesses good binding and diluent properties, but its disintegrating power remains limited, and its flow properties are mediocre, which requires the use by the formulators of complementary excipients (VISAVARUNGROJ N, RENON J. P., (1992) Pharm. Tech. Int. JAN/FEB p26-32).
Moreover, the implementation of this complex and expensive process does not enable a good control of the granulometry, which causes a large variation in the properties of this product.
More recently, another process for producing directly compressible pre-gelatinised starch has been proposed, in the patent EP 402 186. The product produced, marketed under the name of SEPISTAB.RTM. ST 200, results from a moist granulation of natural starch by a starch solution. This process, which requires a large proportion of natural starch, leads to a powder, the granules of which are flaky and fragile, which is detrimental to the use of this powder in high rate industrial machines, which generate a significant physical stress.
Consequently, none of the prior art processes enable, in an acceptable economic way, starch compositions simultaneously having good diluent and disintegrating properties to be produced.